A research program will be undertaken by the applicant, Michelle Lai, MD, MPH, in the Division of Gastroenterology at the Beth Israel Deaconess Medical Center (BIDMC). Dr. Lai has had substantial clinical research exposure during her medical school, residency and Gastroenterology fellowship, during which she showed impressive productivity and commitment to an academic career in patient oriented research. Drs. Nezam H. Afdhal and Detlef Schuppan, Associate Professors in the Division of Gastroenterology, BIDMC and Dr. John B. Wong, Professor of Medicine in the Division of Clinical Decision Making, Informatics and Telemedicine at the Tufts Medical Center will serve as mentors. Approximately 30 million Americans are affected with Nonalcoholic fatty liver disease (NAFLD) with spectrum of disease ranging from benign simple steatosis to the more concerning steatohepatitis (NASH). The limitations of the current gold standard of liver biopsy are well established. The specific aims of the project are: 1 To characterize the extent to which non-invasive tests of liver fibrosis, metabolism, inflammation/apoptosis, and oxidative stress tests can help improve the ability of clinical predictors to differentiate NASH from simple steatosis in patients with NAFLD;2) To develop and validate a mathematical predictive instrument based on components identified above to predict risk of NASH versus simple steatosis;and 3) To examine the cost-effectiveness of alternative diagnostic approaches including liver biopsy, single predictors, and combinations of predictors including the multivariate model from Aim 2 to distinguish NASH versus simple steatosis. In addition to the research component, the applicant will undertake didactic courses at the Harvard School of Public health and the Tufts Sackler Graduate School of Biomedical Sciences. This will include formal training in decision analysis, prediction and predictive modeling, cost-effectiveness and cost-benefit analysis, pharmacoeconomics, data mining, database and genetics and genomics. The very substantial research, educational, and clinical resources of the BIDMC Gastroenterology Division and Liver Center, Harvard School of Public Health, Tufts Sackler School and Division of Clinical Decision Making will be committed to Dr. Lai to ensure successful attainment of the goals of this award. PUBLIC HEALTH RELEVANCE: Limitations of liver biopsy have been well established. This study on noninvasive approaches differentiate simple steatosis from NASH is imperative given the scope of the epidemic. It will give a predictive instrument for NASH as well as answer health policy questions that will have a substantial impact on the national health care budget, clinical practice and on patient health.